TRANSFORME EDİCİ BÜYÜME FAKTÖRÜ BETA-3 (TGF-β3) YÜKLÜ NANOPARTİKÜLLERİN SIÇANLARDA AŞİL TENDON İYİLEŞMESİ ÜZERİNE ETKİLERİNİN ARAŞTIRILMASI

Abstract

Achilles tendon is the strongest tendon in the human body, and is one of the most frequently injured tendons . TGF-β3 was shown to induce tendinogenesis in embriyonic stem cells; but it’s in vivo effects are not long-lasting. The aim of this thesis project is to evaluate the effect of TGF-β3 on healing after achilles tendon injury. For this purpose, on a unilateral achilles tendon injury model in rats, the in vivo efficacy of TGF-β3 loaded polylactic-co-glycolic acid-b- polyethylene glycol (PLGA-b-PEG) nanoparticles has been evaluated. 80 male Sprague-Dawley rats were divided into 4 groups: control (C), empty chitosan film (Ch), chitosan film containing free TGF-β3 (ChT) and chitosan film containing TGF-β3 loaded nanoparticles (ChN). 40 rats were sacrified in the 3rdweek, and the remaining 40 in the 6th week; therefore 8 experimental groups were formed with 10 rat in each. Tendons were evaluated biomechanically, histologically (Bonar and Movin scores), immunohistochemically (type I and type III collagen); and gene expression analysis was done for COL1A1, COL3A1, scleraxis and tenomodulin by using real time polymerase chain reaction (RT-PCR) technique. Histologic analysis showed better scores for both ChT and ChN groups. Biomechanically, ChT group had a higher maximum load on 3rd week, and ChN group had higher maximum stress on 6th week. Immunohistochemically, ChN group was shown to express higher amounts of type III collagen on 3rd week and type I collagen on 6th week. Gene expression for COL1A1 was higher for ChT and ChN on 3rd week, COL3A1 was only higher in ChN group. Our results indicate that TGF-β3 loaded PLGA-b-PEG nanoparticles, which have a longer duration of action, show positive effects on achilles tendon healing in a rat model.